More than 14 million people in the United States have diabetes. All people with diabetes are at risk of retinal complications. However, people with type I, i.e., insulin-dependent, diabetes, face a greater risk of severe vision loss than people with type II, i.e., non-insulin dependent, diabetes. Initially, the high blood glucose level in diabetic people causes an increase in growth factors in their eyes. This condition is known as the “pre-diabetic retinopathy stage” and can lead to retinopathy, if not prophylactically treated.
Retinopathy will affect the majority of diabetic people to some extent during their lifetimes (Anonymous, MMWR 42(10): 191-195 (1993)). It is the leading cause of blindness in Americans of age 20 to 74 today and is expected to impair vision in approximately one-third of diabetic people in the United States. Each year in the United States, as many as 40,000 new cases of blindness occur among diabetic people. Diabetic people are 25 times more likely than the general population to become blind due to retinopathy.
Diabetic retinopathy (DR) is recognized as a retinal vascular disorder that includes: (1) excess capillary permeability, (2) vascular closure, and (3) proliferation of new vessels (Council NAE. Report of the Retinal Diseases Panel. Vision Research: A National Plan 1994-1998. Vol. NIH Publication No. 93-3186. Bethesda: Public Health Service, 1993:11-109.). DR is recognized to consist of two (2) stages: nonproliferative and proliferative. In the nonproliferative stage the disease is characterized by a loss of retinal capillary pericytes, thickening of the basement membrane and development of microaneurysms, dot-blot hemorrhages, and hard exudates. In the proliferative stage the disease patients develop extensive neovascularization, vessel intrusion into the vitreous, bleeding and fibrosis with subsequent retinal traction, which leads to severe vision impairment (Klein et al., Opthalmol, (1984); 91:10-17. Merimee T. J., New England Journal of Medicine 322:978-987(1990)).
While the pathological stages of diabetic retinopathy are well-described, the molecular events underlying diabetic retinopathy are poorly understood. This is due, in part, to the fact that the disease progresses over ten to thirty years, depending on a given individual. Tight control of glycemia and hypertension and ophthalmic screening of diabetics appears beneficial in preventing the disease. Current treatment consists of regular observation by an ophthalmologist, laser photocoagulation and vitrectomy.
Macular edema threatening or involving the macular center is treated with focal macular photocoagulation. Small (50 microns in diameter), mild-intensity laser bums are targeted at areas of leakage in the macula (Murphy, Amer. Family Physician 51(4): 785-796 (1995)). If the macular edema persists, retreatment may be necessary. Patients with severe to very severe nonproliferative retinopathy and patients, who are at high risk for proliferative retinopathy or who already have early or advanced proliferative retinopathy, are treated with scatter or panretinal photocoagulation. Panretinal photocoagulation (PRP) involves 1,500-2,000 laser bums, which are 500 microns in diameter, in the midperipheral and peripheral portion of the retina (Murphy (1995), supra). In light of the prevalence of DR, there remains a need for therapeutic and prophylactic treatments for this disease.